Lungs Sense Bitterness Using a Little Bit of Tongue

More than a dozen of
the taste receptors found on the tongue also have been discovered in human
lungs, and manipulating them could help people with asthma, researchers report.

Surprised scientists
found the receptors by accident during a study of molecules in human lung
muscle that regulate airway contraction and relaxation. The discovery "was
so unexpected that we were at first quite skeptical ourselves," said
researcher Stephen Liggett, a pulmonologist at the University of Maryland
School of Medicine and director of its Cardiopulmonary Genomics Program.

Specifically, the
investigators discovered proteins responsible for tasting
bitterness. On the tongue, these receptors are clustered in taste buds,
which send signals to the brain. In the lung, the receptors are not clustered
in buds and do not send signals to the brain, but they do respond to substances
that have a bitter taste. All in all, 17 of the 25 known types of bitter-taste
receptors were seen in the lung. No other kinds of taste receptors were found
there.

"Finding these
receptors in a place where they weren't supposed to be was pretty
exciting," Liggett said.

Wheezing mice

To find out what
these receptors do in the lung, Liggett and his colleagues exposed bitter
compounds to human and mouse airways and to mice with asthma. In asthma, these
airways contract, impeding the flow of air, causing wheezing
and shortness of breath.

Since most
plant-based poisons are bitter, the researchers expected the purpose of the
lung's taste receptors would be to warn against poisons.

"I initially
thought the bitter-taste receptors in the lungs would prompt a 'fight or
flight' response to a noxious inhalant, causing chest tightness and coughing so
you would leave the toxic environment," Liggett said. "But that's not
what we found."

Unexpectedly, when
the researchers tested a few standard bitter substances against these receptors,
"it turns out that the bitter compounds worked the opposite way from what
we thought," Liggett said. "They all opened the airway more
profoundly than any known drug that we have for treatment
of asthma or chronic obstructive pulmonary disease."

While compounds
known as beta-agonists that are normally used in inhalers for asthma and
chronic obstructive pulmonary disease "work fairly well, bitter compounds
worked three to four times better in terms of extent of relaxation they could
provide," Liggett told LiveScience. "At first it looked like some
kind of mistake on our end — that maybe the muscle we tested was damaged and
was relaxing as it was dying — but that wasn't the case."

As to why bitter
compounds had the opposite effect of what researchers expected, "it turns
out bacteria make a bitter substance as they infect the lungs," Liggett
said. "Thus, during bronchitis or pneumonia, the body can respond by
opening the airways, helping the individual to breathe and to clear the
cellular debris, mucus and bacteria from the infection."

Bitter treatment

Asthma and chronic
obstructive pulmonary disease together affect 300 million people worldwide, and
these numbers are growing. According to the American Lung Association, asthma
affects nearly 23 million people in the United States, including 7 million
children, and chronic obstructive pulmonary disease is the fourth-leading cause
of death in the nation. [Related: Burger
and Fries Worsen Asthma]

There are thousands
of bitter compounds that, in appropriate doses, are not toxic, and someday the
new knowledge may be able to help people with lung problems breathe easier,
Liggett said. Quinine and chloroquine, which are very bitter and have been used
to treat completely different diseases such as malaria, opened contracted
airways profoundly in laboratory models. Even saccharin, which has a bitter
aftertaste, was effective at activating these receptors.

"New drugs to
treat asthma, emphysema or chronic bronchitis are needed," Liggett
explained. "This could replace or enhance what is now in use, and
represents a completely new approach."

At least half of all
asthma patients do not have adequate control of the disease through the drugs
that are currently available.

"Given so many
known bitter compounds — at least 10,000 — we have a great opportunity to
quickly find a new drug for treating asthma and chronic obstructive lung
disease," Liggett said. “We are now screening a large number of bitter
compounds to find the ones that are most potent in dilating the airways. From
these, we will build compounds that are modifications of these and continue
testing. Once we settle on a few compounds, we will formulate them for delivery
by aerosol from an inhaler and begin clinical trials.”

Liggett cautioned
that eating bitter foods or compounds would not help in treating asthma.
"Based on our research, we think that the best drugs would be chemical
modifications of bitter compounds, which would be aerosolized and then inhaled
into the lungs with an inhaler," he said.

The researchers found aerosol forms of bitter
substances could relax the airways of mice with asthma.

Charles Q. Choi is a contributing writer for Live Science and Space.com. He covers all things human origins and astronomy as well as physics, animals and general science topics. Charles has a Master of Arts degree from the University of Missouri-Columbia, School of Journalism and a Bachelor of Arts degree from the University of South Florida. Charles has visited every continent on Earth, drinking rancid yak butter tea in Lhasa, snorkeling with sea lions in the Galapagos and even climbing an iceberg in Antarctica.